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Hybrid Cell Analysis System to Assess Structural and Contractile Changes of Human iPSC-Derived Cardiomyocytes for Preclinical Cardiac Risk Evaluation
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Osimertinib is associated with reversible and dose-independent cancer therapy-related cardiac dysfunction

Kei Kunimasa1, Toru Oka2, Satoshi Hara3

  • 1Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.

Lung Cancer (Amsterdam, Netherlands)
|December 5, 2020
PubMed
Abstract

Insights

Osimertinib use in EGFR-mutated non-small cell lung cancer patients can cause cardiac dysfunction. This cancer therapy-related cardiac dysfunction (CTRCD) is reversible with treatment modification and may be predicted by a history of heart disease.

Area of Science:

  • Oncology
  • Cardiology
  • Pharmacology

Background:

  • Osimertinib is a targeted therapy for EGFR-mutated non-small cell lung cancer (NSCLC).
  • Cancer therapy-related cardiac dysfunction (CTRCD) is a potential risk associated with cancer treatments.
  • The specific cardiac risks of osimertinib in NSCLC patients require further clinical characterization.

Purpose of the Study:

  • To investigate the clinical features of CTRCD in patients with EGFR-mutated NSCLC treated with osimertinib.
  • To assess the incidence and reversibility of CTRCD.
  • To identify predictors of CTRCD in this patient population.

Main Methods:

  • Retrospective evaluation of 183 advanced EGFR-mutated NSCLC patients receiving osimertinib monotherapy.
  • Serial echocardiography to assess longitudinal changes in left ventricular ejection fraction (LVEF) in 58 patients.
  • Multivariate analysis to identify predictors of CTRCD.

Main Results:

  • 8.7% of patients experienced a significant decrease in LVEF (≥10 units), and 4.4% met CTRCD criteria.
  • Mean LVEF significantly decreased post-osimertinib treatment (69% to 66%, p<0.001).
  • History of heart disease was a significant predictor of CTRCD (ORR 4.97, P=0.022).

Conclusions:

  • Osimertinib is associated with a risk of CTRCD in EGFR-mutated NSCLC patients.
  • CTRCD appears to be dose-independent and reversible upon drug discontinuation, dose reduction, or switching EGFR inhibitors.
  • Prompt identification and management of CTRCD are crucial for patients receiving osimertinib.
Keywords:
CTRCDEGFRcardio-oncologyosimertinib

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